Addictive substances take control of the brain's natural learning mechanisms, by activating reward mechanisms that reinforce behaviors associated with drug taking. But how much is known about these mechanisms at the levels of behavior, of brain systems, and of cellular pharmacology. However, there is a large gap in our understanding of the dynamic relationships between cellular plasticity and behavior. We will explore reward-related neural plasticity at the microscopic and mesoscopic scale using neuronal networks cultured on multi-electrode arrays with tong-term stimulation and recording. Reward-related neuromodulators will be applied to the networks to study their influence on physiological and morphological plasticity, in the context of the Neurally-Controlled Animal paradigm, in which network activity controls the behavior of a simulated animal. Time-lapse imaging, using both 2-photon and wide-field videomicroscopy, will allow us to observe in detail cellular and network-level morphological dynamics related to learning, memory, and addiction. By creating an in-vitro reward system, we can observe and manipulate reward related plasticity in much greater detail than possible in animals or people. By embodying the cultured networks, we can bring in-vitro studies of neural plasticity to the behavioral level, and enhance their relevance to addiction mechanisms in vivo.